Structure-Based Virtual Screening and In Vitro Evaluation of New Trypanosoma cruzi Cruzain Inhibitors

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AudienciaPúblico en generales_ES
CoberturaMéxicoes_ES
Fecha de ingreso2026-10-05T16:33:07Z
Fecha de publicación2019-01-01
ResumenChagas disease (CD), or American trypanosomiasis, causes more than 10,000 deaths per year in the Americas. Current medical therapy for CD has low efficacy in the chronic phase of the disease and serious adverse effects; therefore, it is necessary to search for new pharmacological treatments. In this work, the ZINC(15) database was filtered using the N-acylhydrazone moiety and a subsequent structure-based virtual screening was performed using the cruzain enzyme of Trypanosoma cruzi to predict new potential cruzain inhibitors. After a rational selection process, four compounds, Z2 (ZINC9873043), Z3 (ZINC9870651), Z5 (ZINC9715287), and Z6 (ZINC9861447), were chosen to evaluate their in vitro trypanocidal activity and enzyme inhibition. Compound Z5 showed the best trypanocidal activity against epimatigote (IC50 = 36.26 +/- 9.9 mu M) and trypomastigote (IC50 = 166.21 +/- 14.5 mu M and 185.1 +/- 8.5 mu M on NINOA and INC-5 strains, respectively) forms of Trypanosoma cruzi. In addition, Z5 showed a better inhibitory effect on Trypanosoma cruzi proteases than S1 (STK552090, 8-chloro-N-(3-morpholinopropyl)-5H-pyrimido{[}5,4-b]-indol-4-amine), a known cruzain inhibitor. This study encourages the use of computational tools for the rational search for trypanocidal drugs.es_ES
Doihttps://doi.org/10.3390/ijms20071742es_ES
URIhttps://riuat.uat.edu.mx/handle/123456789/4959
Idiomaenes_ES
EditorialMDPIes_ES
RelaciónInternational Journal of Molecular Scienceses_ES
URL relacionadohttps://doi.org/10.3390/ijms20071742es_ES
DerechosAcceso abierto (Metadatos de producción científica)es_ES
Licenciahttp://purl.org/coar/access_right/c_abf2es_ES
FuenteInternational Journal of Molecular Sciences
Palabra claveTrypanosoma cruzies_ES
Palabra clavemolecular dockinges_ES
Palabra clavecruzaines_ES
Palabra claveZinc(15)es_ES
Palabra claveinhibitorses_ES
TítuloStructure-Based Virtual Screening and In Vitro Evaluation of New Trypanosoma cruzi Cruzain Inhibitorses_ES
TipoArtículoes_ES
ArbitradoHa sido Arbitradoes_ES
AutorHerrera-Mayorga, Veronica
AutorLara-Ramirez, Edgar E.
AutorChacon-Vargas, Karla F.
AutorAguirre-Alvarado, Charmina
AutorRodriguez-Paez, Lorena
AutorAlcantara-Farfan, Veronica
AutorCordero-Martinez, Joaquin
AutorNogueda-Torres, Benjamin
AutorReyes-Espinosa, Francisco
AutorBocanegra-Garcia, Virgilio
AutorRivera, Gildardo
AutorHerrera-Mayorga, Veronicaes_ES
AutorLara-Ramirez, Edgar E.es_ES
AutorChacon-Vargas, Karla F.es_ES
AutorAguirre-Alvarado, Charminaes_ES
AutorRodriguez-Paez, Lorenaes_ES
AutorAlcantara-Farfan, Veronicaes_ES
AutorCordero-Martinez, Joaquines_ES
AutorNogueda-Torres, Benjamines_ES
AutorReyes-Espinosa, Franciscoes_ES
AutorBocanegra-Garcia, Virgilioes_ES
AutorRivera, Gildardoes_ES
InstituciónUniversidad Autónoma de Tamaulipas
InstituciónUniversidad Autónoma de Tamaulipases_ES
Número7es_ES
URL relacionadahttps://doi.org/10.3390/ijms20071742
Tipo de artículoIndexado
Tipo de artículoIndexadoes_ES
Volumen20es_ES

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